Despite recent strides in the molecular and biophysical scrutiny of ligand-gated ion channels, the developmental regulation of neuronal receptors has largely eluded analysis. Previous studies by this laboratory revealed that nicotinic acetylcholine receptors (nAChRs) expressed by central and peripheral neurons are profoundly altered during neuronal development, concurrent with synaptogenesis. In view of the complex and reciprocal nature of synapse formation, the investigators hypothesize that the induction and maturation of transmitter gated channels results from coordinate regulation by both presynaptic input and target contact. Aim I examines the role of presynaptic input in the developmental regulation of nAChRs. The investigators will test if presynaptic activity and/or anterograde signals are required for the expression of mature nAChR channel subtypes. The analysis of input-induced changes in nAChRs combines molecular and biophysical approaches to map nAChR channel distribution and dissect nACnR subunit composition. A candidate presynaptic regulator of neuronal nAChRs has been identified. They will test for changes in nAChR expression in response to this factor and related molecules. Aim II explores the extent of target-induced changes in nAChRs in detail, examining the mechanism(s) by which target innervation and retrograde signals control the biophysical profile, subunit composition and cellular distribution of neuronal nAChR channels.